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ID PMID Title PublicationDate abstract
27846761 Prognostic factors of methotrexate-associated lymphoproliferative disorders associated wit 2017 Sep OBJECTIVES: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. METHODS: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. RESULTS: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein-Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. CONCLUSIONS: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.
27988432 TLRs, future potential therapeutic targets for RA. 2017 Feb Toll like receptors (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients.
26547912 A Systematic Review of Factors Associated with Non-Adherence to Treatment for Immune-Media 2015 Nov BACKGROUND: Non-adherence impacts negatively on patient health outcomes and has associated economic costs. Understanding drivers of treatment adherence in immune-mediated inflammatory diseases is key for the development of effective strategies to tackle non-adherence. OBJECTIVE: To identify factors associated with treatment non-adherence across diseases in three clinical areas: rheumatology, gastroenterology, and dermatology. DESIGN: Systematic review. DATA SOURCES: Articles published in PubMed, Science Direct, PsychINFO and the Cochrane Library from January 1, 1980 to February 14, 2014. STUDY SELECTION: Studies were eligible if they included patients with a diagnosis of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, or psoriasis and included statistics to examine associations of factors with non-adherence. DATA EXTRACTION: Data were extracted by the first reviewer using a standardized 23-item form and verified by a second/third reviewer. Quality assessment was carried out for each study using a 16-item quality checklist. RESULTS: 73 studies were identified for inclusion in the review. Demographic or clinical factors were not consistently associated with non-adherence. Limited evidence was found for an association between non-adherence and treatment factors such as dosing frequency. Consistent associations with adherence were found for psychosocial factors, with the strongest evidence for the impact of the healthcare professional-patient relationship, perceptions of treatment concerns and depression, lower treatment self-efficacy and necessity beliefs, and practical barriers to treatment. CONCLUSIONS: While examined in only a minority of studies, the strongest evidence found for non-adherence were psychosocial factors. Interventions designed to address these factors may be most effective in tackling treatment non-adherence.
27920363 Detection of imprinting effects for qualitative traits on X chromosome based on nuclear fa 2018 Aug Methods for detecting imprinting effects have been developed primarily for autosomal markers. However, no method is available in the literature to test for imprinting effects on X chromosome. Therefore, it is necessary to suggest methods for detecting such imprinting effects. In this article, the parental-asymmetry test on X chromosome (XPAT) is first developed to test for imprinting for qualitative traits in the presence of association, based on family trios each with both parents and their affected daughter. Then, we propose 1-XPAT to deal with parent-daughter pairs, each with one parent and his/her affected daughter. By simultaneously considering family trios and parent-daughter pairs, C-XPAT (the combined test statistic of XPAT and 1-XPAT) is constructed to test for imprinting. Further, we extend the proposed methods to accommodate complete (with both parents) and incomplete (with one parent) nuclear families having multiple daughters of which at least one is affected. Simulation results demonstrate that the proposed methods control the size well, irrespective of the inbreeding coefficient in females being zero or non-zero. By incorporating incomplete nuclear families, C-XPAT is more powerful than XPAT using only complete nuclear families. For practical use, these proposed methods are applied to analyse the rheumatoid arthritis data and Turner's syndrome data.
26846135 Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since 2016 Apr This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan.
26643105 The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an ant 2015 Dec 4 BACKGROUND: Lubricin/proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 has a homeostatic multifaceted role in the joint. PRG4 intra-articular treatment retards progression of cartilage degeneration in pre-clinical posttraumatic osteoarthritis models. The objective of this study is to evaluate the binding of recombinant human PRG4 (rhPRG4) and native human PRG4 (nhPRG4) to toll-like receptors 2 and 4 (TLR2 and TLR4) and whether this interaction underpins a PRG4 anti-inflammatory role in synovial fluid (SF) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: rhPRG4 and nhPRG4 binding to TLR2 and TLR4 was evaluated using a direct enzyme linked immunosorbent assay (ELISA). Association of rhPRG4 with TLR2 and TLR4 overexpressing human embryonic kidney (HEK) cells was studied by flow cytometry. Activation of TLR2 and TLR4 on HEK cells by agonists Pam3CSK4 and lipopolysaccharide (LPS) was studied in the absence or presence of nhPRG4 at 50, 100 and 150 μg/ml. Activation of TLR2 and TLR4 by OA SF and RA SF and the effect of nhPRG4 SF treatment on receptor activation was assessed. PRG4 was immunoprecipitated from pooled OA and RA SF. TLR2 and TLR4 activation by pooled OA and RA SF with or without PRG4 immunoprecipitation was compared. RESULTS: rhPRG4 and nhPRG4 exhibited concentration-dependent binding to TLR2 and TLR4. rhPRG4 associated with TLR2- and TLR4-HEK cells in a time-dependent manner. Co-incubation of nhPRG4 (50, 100 and 150 μg/ml) and Pam3CSK4 or LPS reduced TLR2 or TLR4 activation compared to Pam3CSK4 or LPS alone (p <0.05). OA SF and RA SF activated TLR2 and TLR4 and nhPRG4 treatment reduced SF-induced receptor activation (p <0.001). PRG4 depletion by immunoprecipitation significantly increased TLR2 activation by OA SF and RA SF (p <0.001). CONCLUSION: PRG4 binds to TLR2 and TLR4 and this binding mediates a novel anti-inflammatory role for PRG4.
25854488 Antinuclear antibody (ANA) testing in patients treated with biological DMARDs: is it usefu 2015 Apr The appearance of biologic agents for the treatment of diverse autoimmune diseases in particular rheumatoid arthritis at the end of the 1990s changed the treatment of these patients. With the introduction of new agents in the treatment of rheumatic diseases, we started to notice the presence of new and sometimes unexpected adverse events. It is well recognized that infections are the main concern with these types of treatments; however, the occurrence of autoimmune abnormalities is also seen and its gaining perhaps more attention as the use of these agents is increasing. The first clinical trials of anti-tumor necrosis factor-α (anti-TNFα) inhibitors showed an increase of antinuclear and anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies in patients treated with these agents. In this paper, we review the frequency of these autoantibodies in patients treated with biologic agents, particularly anti-TNF-α inhibitors, and its correlation with autoimmune processes as well as the clinical relevance of such findings.
27866531 [Effect of 10-Hydroxycamptotbecine on the proliferation of human Fibroblast-like Synoviocy 2016 Nov 15 Objective: To study the effect of 10-Hydroxycamptothecine (10-HCPT) on the proliferation and apoptosis of human Fibroblast-like Synoviocyte (FLS) with Rheumatoid Arthritis (RA). Methods: Different concentrations of 10-HCPT and Methotrexate (MTX) were used to treat FLS cells in RA and Osteoarthritis (OA) for different time (24, 48, and 72 hours), and FLS cells without 10-HCPT and MTX were served as the control group. CCK-8 assay were applied to determine the proliferation of FLS cells, Annexin-V APC/7-AAD staining were used to detect the apoptosis of FLS cells. Results: The survival rate of FLS cells were (66.68±0.48) %, 48 h; (60.09±0.95) %, 72 h and (44.05±1.29) %, 48 h; (30.63±1.79) %, 72 h, when the concentrations were 1.0 μg/ml and 10.0 μg/ml in 10-HCPT group. Compared with the control group, the survival rate of FLS cells in RA and OA both declined in treatment groups with different concentrations of 10-HCPT and MTX. With the extension of time, the survival rate of FLS cells declined significantly. Compared with the MTX group, there were no obvious differences in 10-HCPT group with 1.0 μg/ml. But the concentration of 10.0 μg/ml of 10-HCPT group showed obviously difference in the proliferation of FLS cells. The apoptosis rate of FLS cells were (66.68±0.48) %, 48 h; (60.09±0.95) %, 72 h and (44.05±1.29) %, 48 h; (30.63±1.79) %, 72 h, when the concentrations were 1.0 μg/ml and 10.0 μg/ml in 10-HCPT group. Compared with the control group, two concentrations of 10-HCPT and MTX induced higher apoptosis in FLS cells with RA and OA; with the extension of time (72 h), the rate of apoptosis was significantly enhanced (P<0.05). When FLS cells with RA were treated for 48 h, apoptosis of 10-HCPT group was higher than that of MTX group. The 10.0 μg/ml of 10-HCPT had the highest effect. Conclusion: Compared with MTX, 10-HCPT had the higher efficacy of inhibiting proliferation and promoting apoptosis in FLS cells.
27966068 Body mass does not impact the clinical response to intravenous abatacept in patients with 2017 Apr Some evidences suggest that obesity impairs the effectiveness of TNF inhibitors. We examined the impact of body mass index (BMI) on the clinical effectiveness of abatacept in rheumatoid arthritis (RA) patients. This is a pooled analysis of 10 prospective cohorts of RA patients. All patients with available BMI were included in this study. The primary endpoint was drug retention of abatacept in the different BMI categories. Multivariable Cox regression was used to estimate hazard ratios (HRs) for drug discontinuation. A secondary endpoint was EULAR/LUNDEX response rates at 6/12 months. Of the 2015 RA patients initiating therapy with IV abatacept, 380 (18.9%) were classified as obese. Obese patients had more functional disability, and were less often RF positive. The median abatacept retention time was 1.91 years for obese RA patients compared to 2.12 years for non-obese patients (p = 0.15). The risk of abatacept discontinuation was not significantly different for overweight (HR 1.03 (95% CI 0.89-1.19)), or for obese (HR 1.08 (95% CI 0.89-1.30)) compared to normal-weight patients. Rheumatoid factor positivity reduced the risk of abatacept discontinuation (HR 0.83 (95% CI 0.72-0.95)), while previous biologic therapy was positively associated with drug interruption (HRs increasing from 1.68 to 2.16 with the line of treatments). Obese and non-obese patients attained similar rates of EULAR/LUNDEX clinical response at 6/12 months. Drug retention and clinical response rates to abatacept do not seem to be decreased by obesity in RA patients.
26345633 Retention of the second-line biologic disease-modifying antirheumatic drugs in patients wi 2015 Oct This study aimed to investigate the retention of the second-line biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis patients failing their first tumor necrosis factor alpha inhibitor (TNFi). Data was extracted from the Slovenian registry (BioRx.si) on December 15, 2012. Baseline patient characteristics were compared between second-line TNFi and non-TNFi, and potential confounders were identified by the means of binary logistic regression. Differential drug retention was assessed using the Kaplan-Meier method and crude and inverse probability-weighted Cox proportional hazards regression models (Cox model). Two hundred thirty-eight out of 688 patients who received a TNFi as the first biologic were switched to another biologic: 130 to a second-line TNFi and 108 to either rituximab (31.5 %) or tocilizumab (68.5 %) (non-TNFi). Disease activity at starting second-line bDMARD and stopping the first-line TNFi due to either lack of effectiveness or loss of effectiveness were identified as potential confounders. There appears to be a statistically significant retention advantage of the non-TNFi over the second-line TNFi (log rank test, p = 0.000). This advantage is retained even after taking into account the possible effect of confounders which was tested using the inverse probability-weighted Cox model [hazard ratio (HR) 4.39; 95 % confidence interval (CI) 2.62-8.01, p < 0.001]. After the first-line TNFi's failure, a second-line TNFi is more likely to fail earlier than non-TNFi.
27252272 Sweet but dangerous - the role of immunoglobulin G glycosylation in autoimmunity and infla 2016 Jul Glycosylation is well-known to modulate the functional capabilities of immunoglobulin G (IgG)-mediated cellular and humoral responses. Indeed, highly sialylated and desialylated IgG is endowed with anti- and pro-inflammatory activities, respectively, whereas fully deglycosylated IgG is a rather lame duck, with no effector function besides toxin neutralization. Recently, several studies revealed the impact of different glycosylation patterns on the Fc part and Fab fragment of IgG in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we provide a synoptic update summarizing the most important aspects of antibody glycosylation, and the current progress in this field. We also discuss the therapeutic options generated by the modification of the glycosylation of IgG in a potential treatment for chronic inflammatory diseases.
25769795 Domain-specific transition questions demonstrated higher validity than global transition q 2015 Jun OBJECTIVES: Estimates of minimal clinically important differences in health measures may be affected by the anchor used. We examined if domain-specific transition questions had higher construct validity than global health transition questions as anchors for measures in a given domain. STUDY DESIGN AND SETTING: In a prospective study of 249 patients with rheumatoid arthritis, we examined changes in pain, physical function, joint swelling, stiffness, fatigue, and depression with treatment. We related these changes to a domain-specific transition question, global arthritis transition question, and the Short Form-36 (SF-36) health transition item. RESULTS: Changes in all six clinical measures were more highly correlated with the domain-specific transition questions than with the global arthritis question and SF-36 transition question. Discrimination between patients who improved or not was also better using domain-specific questions. Estimates of minimal clinically important improvement (MCII) differed with the anchor when these were based on mean changes. MCII estimates from receiver operating characteristic curve analysis were not influenced by the choice of anchor when anchors had high agreement. CONCLUSION: Domain-specific transition questions had higher construct validity as anchors for determining clinically important differences in health measures focused on a single domain than either global disease or general health transition questions.
27879510 Clinical and Radiographic Outcomes of C1 Laminectomy Without Fusion in Patients With Cervi 2016 Dec PURPOSE: A retro-odontoid pseudotumor that is not associated with rheumatoid arthritis or hemodialysis is clinically rare. The majority of surgeons select transoral resection as the surgical treatment, often followed by posterior fusion or posterior decompression and fusion. In contrast, some authors have reported success with simple decompression without posterior stabilization in cases where atlanto-axial instability (AAI) is either absent or minor. In this study, we have evaluated the clinical and radiographic outcomes of C1 laminectomy without fusion as the surgical treatment for patients with cervical myelopathy that is associated with a retro-odontoid pseudotumor. METHODS: A retrospective chart review was conducted on 10 patients who underwent C1 laminectomy without fusion for cervical myelopathy associated with a retro-odontoid pseudotumor. RESULTS: The average follow-up time was 29 months. All cases were graded as Ranawat grade 3a or 3b. After surgery, myelopathy improved in all of the patients. In 2 patients, the atlas-dens interval increased in the flexed position; however, this did not result in any clinical problems. The size of the retro-odontoid mass (measured on magnetic resonance images at least 12 mo after surgery) decreased in 4 of the 10 cases. CONCLUSIONS: AAI progression and mass enlargement were our primary concerns for this surgical option; however, C1 laminectomy did not cause severe AAI progression, no patients showed serious mass enlargement, and all patients demonstrated neurological improvement. This surgical strategy is beneficial especially for elderly patients given the risks of other surgical options that use an anterior transoral approach or posterior fusion.
27531604 Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity 2016 Sep 8 Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.
25443193 [SD-OCT As screening test for hydroxychloroquine retinopathy: The «flying saucer» sign]. 2015 Jul CASE REPORTS: Two asymptomatic women treated with hydroxychloroquine 200mg every day for 8 and 16 years developed retinal toxicity. DISCUSSION: Patient 1 was found to have a normal fundus and autofluorescence examination. Patient 2 was found to have a completely normal fundus examination. Fluorescein angiography shows parafoveal hyperfluorescence, and autofluorescence shows a minimal decrease in signal in the same region. In both patients the SD-OCT shows disruption of the ellipsoid zone in parafoveal region («flying saucer» sign). SD-OCT findings in the retina can identify hydroxychloroquine retinopathy in asymptomatic patients.
24431398 Effectiveness of TNF inhibitor switch in RA: results from the national Swedish register. 2015 May BACKGROUND: Switching to a second tumour necrosis factor inhibitor (TNFi) after discontinuation of a first in rheumatoid arthritis (RA) is a common strategy. The reason for the switch from the first TNFi could potentially influence the response to therapy. Data on direct comparisons between TNFi after switching are limited. METHODS: The national Swedish register was used. RA patients who switched to a second TNFi (infliximab, etanercept or adalimumab) after failure of a TNFi as first-ever biologic were identified. Effectiveness of treatment was compared across the three drugs according to the first TNFi used, the reason for discontinuing and the drug survival. Drug survival across TNFi used as second biologic was compared. RESULTS: Half of all patients starting infliximab, adalimumab or etanercept during the period 2005-2012 discontinued treatment for various reasons. Of these patients, a third switched within 2 months to a second TNFi (infliximab, etanercept or adalimumab). Around 35% of all patients achieved low disease activity or remission at 6 months. Regarding the switching strategy, best results were observed among patients who switched from infliximab to etanercept because of (secondary) inefficacy. Etanercept as second TNFi was associated with longer drug survival compared with infliximab. CONCLUSIONS: Switching to a second TNFi after the failure of the first may lead to good clinical results. The inter-drug differences in drug survival on the second TNFi mirror those reported previously for the first TNFi, suggesting that these differences are not solely due to channelling bias.
25609412 Association of hyperlipidaemia, inflammation and serological status and coronary heart dis 2016 Feb OBJECTIVE: To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA). METHODS: The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles. RESULTS: There were 37,568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48). CONCLUSIONS: In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
25553695 Formulation and evaluation of mini-tablets-filled-pulsincap delivery of lornoxicam in the 2015 Jan In this present research work, we have designed a pulsincap formulation comprising mini-tablets, which to the best of our knowledge this combination has not been reported yet. We successfully combined the advantages of mini-tablets technology to meet the optimized requirements of our pulsincap formulation. Our main aim was to target lornoxicam to treat rheumatoid arthritis as per the chronotherapeutic pattern of the disease. Directly compressing method was used to prepare mini-tablets. The drug, polymers and combine mixtures of drug and polymers was evaluated for pre-formulation testing. Prepared mini-tablets were also evaluated for physicochemical, dissolution and stability studies. From FTIR and DSC evaluation, we found no interaction between the drug and polymers used. For mini-tablets, all the physico-chemical parameters were in limit. The mini-tablets of lornoxicam were filled into an insoluble body of capsule, and its opening was sealed by plugging it with a polymer. The complete capsule body after sealing with a cap was given enteric coating. Different polymers in various concentrations were used as a plug, to identify the most suitable which gives a complete lag time of 5 hours when combined with 5% CAP coating. HPMC-K100M in 30% and sodium alginate in 40% concentrations were identified as the most suitable plugs. Our optimized pulsincap formulations releases lornoxicam after a lag time of 5 hrs and maximum portion of the drug will be released in the early morning hours. It was also found to be stable for a period of 6 months as per ICH guidelines.
27265072 Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum. 2016 May The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus.
26694020 Population Variations in Rheumatoid Arthritis Treatment and Outcomes, Northern California, 2016 Winter OBJECTIVE: To assess variations in rheumatoid arthritis treatment and outcomes at the community level from 1998 through 2009. METHODS: The study used computerized data from 16 Kaiser Permanente Northern California Medical Centers. Mixed modeling was used to assess patterns across time and clinic. The analysis accounted for patient demographics, clustering of patients within Medical Centers, and repeated measures of patients over time. The metric used to measure drug use, months of use per patient per year, included both users and nonusers in the denominator, to account for both prevalence and duration of use. RESULTS: Assessment was performed of 28,601 patients with rheumatoid arthritis, with all levels of severity. From 1998 through 2009, methotrexate use doubled in the typical patient to include 23% of the time they were observed; sulfasalazine and hydrochloroquine use declined. By 2008 through 2009, leflunomide and antitumor necrosis factor agents were used by the typical patient 4% and 9% of the time, respectively. Between 1998 and 2009, disease-modifying antirheumatic drug use increased in the typical patient from 38% to 63% of the time, and oral prednisone use declined from 23% to 15% of the time, whereas opioid use initially rose but then fell to 23% of the time. No variations over time were observed for the rate of hospitalized pneumonia or opportunistic infection. Variation across clinics, measured by the difference in drug use between clinics at the 75th and 25th percentiles, was lowest for opioids (25% vs 20% of the time) and greatest for infliximab (< 1% to 3%). CONCLUSION: Increased use of disease-modifying antirheumatic drugs and declines in prednisone are encouraging. Opioid use may need intervention.